Birt - Hogg - Dube (BHD) syndrome

Last reviewed 01/2018

Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant disorder that predisposes to fibrofolliculomas, pulmonary cysts, spontaneous pneumothorax and renal neoplasia

BHD is characterized by germline mutations in tumor suppressor FLCN. Inactivation of the remaining FLCN allele in kidney cells drives tumorigenesis

  • in 1977, three physicians for whom the disease was named, Arthur Birt, Georgina Hogg and James Dubé, described a large Canadian family with three generations of individuals who presented with tiny, smooth, flesh-colored papules on the face and neck called fibrofolliculomas (1)

  • most frequently observed clinical manifestation of BHD syndrome is the cutaneous fibrofolliculoma (2,3,4)
    • the dome-shaped, pale yellow to white papules, 2-4 mm in diameter, generally occur on the face including ears and eyelids, neck and upper torso and usually develop after puberty
    • lesions are not painful or pruritic
    • lesions can occur singly or coalesce in a plaque of more than 100 lesions
    • fibrofolliculomas develop in more than 80% of BHD-affected individuals over 25 years of age

  • lung manifestations that occur with high penetrance in BHD syndrome include multiple bilateral pulmonary cysts seen on high-resolution chest computed tomography scans
    • affected members of a BHD family have a 50-fold greater risk (when adjusted for age) for developing spontaneous pneumothorax than their unaffected siblings
      • presence of lung cysts is associated with possible development of pneumothorax
    • about 30% of BHD affected individuals will develop spontaneous pneumothorax, most frequently before the age of 40 years

  • renal neoplasia
    • affected members of BHD families had a 7-fold increased risk for developing renal neoplasia compared to their unaffected siblings
      • BHD patients develop bilateral multifocal renal tumors with a wide spectrum of histologies

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